This application serves as a competitive reapplication ofthe Center of Excellence in Molecular Hematology at the Children's Hospital Boston. The goal of the Center is to facilitate fundamental Studies of the blood system in the two most tractable model organisms~the mouse and zebrafish. Focus on these two systems leverages the advantages of each, while providing the benefits of synergy from parallel developmental and genetic studies. The Center is comprised of 3 cores that serve the users within the Harvard Medical area and elsewhere. CORE A provides consultation and resources for generation of engineered mice and ES cells, distribution of mutant strains and various CRE-expressing and CRE-reporter lines, and assistance in analysis of mouse phenotypes and bone marrow transplantation CORE B is a zebrafish core that supports genetics and developmental studies of hematopoiesis. CORE B maintains numerous mutant zebrafish stocks, and provides education to users. CORE C is a new core focused on technology aimed at supporting research on hematopoietic stem cells and individual blood lineages. One part of CORE C is a fee-for-service flow cytometry core that allows for characterization and isolation of hematopoietic cell populations. A complementary part of CORE C is devoted to technology development and dissemination of methodologies for genomic analyses of small numbers of cells. Specifically, CORE C will validate antibodies for ChlP-sequencing and ChlP-Chip approaches, and improve methods for application of these and other methods (such as genome-wide assessment of DNA methylation) to limited numbers of cells isolated by FACS. CORE C will fulfill an unmet need in the hematology community. In addition to the CORES, the Center will provide an Enrichment Program consisting of workshops and Internet meetings, as well as a Pilot Grant Program designed to support emerging investigators or to recruit new investigators to hematology.